VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00462826
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 49
• Locations: 67
• Arm: 1
• Duration (Months): 62
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent or persistent endometrial cancer. VEGF Trap may stop the growth of endometrial cancer by blocking blood flow to the tumor and by carrying tumor-killing substances directly to endometrial cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Endometrial Carcinoma	Biological: ziv-aflibercept	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Assess the activity of VEGF Trap in patients with recurrent or persistent endometrial cancer, in terms of the frequency of patients who have progression-free survival for at least 6 months after initiating therapy or have objective tumor response.

2. Determine the toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

1. Determine the duration of progression-free survival and overall survival of patients treated with this drug.

OUTLINE:

Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of VEGF-Trap (AFLIBERCEPT, NSC #724770, NCI-Supplied Agent) in the Treatment of Recurrent or Persistent Endometrial Carcinoma
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (aflibercept) Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: ziv-aflibercept; Other Names: aflibercept vascular endothelial growth factor trap VEGF Trap Zaltrap

Outcome Measures

Primary Outcome Measures

1. 6 Month Progression-free Survival [At 6 monthsEvery other cycle during treatment for the first 6 months.]

   Number of participants who survived progression-free for more than 6 months.

2. Objective Tumor Response (RECIST 1.0) [Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years.]

   RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

3. Number of Participants With Incidence of Adverse Events at Least Possibly Related to Study Agent as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [Assessed every cycle while on treatment, 30 days after the last cycle of treatment]

   Adverse events at least possibly related to the study agent.

Secondary Outcome Measures

1. Duration of Progression-free Survival [Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years.]

   Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.

2. Duration of Overall Survival [Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed endometrial carcinoma, meeting both of the following criteria:

• Recurrent or persistent disease

• Refractory to curative therapy or established treatments

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Tumors within a previously irradiated field are designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days after completion of radiotherapy

• Must have received one prior chemotherapeutic regimen for management of endometrial carcinoma (initial treatment may include high-dose therapy, consolidation therapy, or extended therapy administered after surgical or non-surgical assessment)

• Not a candidate for a higher priority GOG protocol

• No history or evidence of primary brain tumor or brain metastases

• GOG performance status (PS) 0-2 (patients who received 1 prior regimen) OR GOG PS 0-1 (patients who received 2 prior regimens)

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Urine protein:creatinine ratio < 1.0 OR urine protein < 1.0 g by 24-hour urine collection

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• SGOT ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• PT/PTT/INR ≤ 1.5 times ULN

• In-range INR (between 2 and 3) allowed if patient is on a stable dose of therapeutic warfarin

• QTc < 500 msec

• No evidence of serious ventricular arrhythmia

• Ventricular tachycardia or ventricular fibrillation must be < 3 beats in a row

• LVEF normal

• Ejection fraction ≥ 50% (for patients who received prior anthracycline, including doxorubicin hydrochloride and/or doxorubicin hydrochloride liposome)

• No clinically significant cardiovascular disease, including any of the following:

• Uncontrolled hypertension, defined as systolic blood pressure (BP) > 140 mm Hg or diastolic BP > 90 mm Hg

• Myocardial infarction or unstable angina within the past 6 months

• NYHA class II-IV congestive heart failure

• Serious cardiac arrhythmia requiring medication

• Peripheral vascular disease ≥ grade 2

• Cerebrovascular accident (i.e., CVA or stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy

• No HIV positivity

• No neuropathy (sensory and motor) > grade 1

• No active infection requiring antibiotics

• No other invasive malignancies or any evidence of other cancer within the past 5 years except for nonmelanoma skin cancer

• No serious nonhealing wound, ulcer, or bone fracture

• No history of abdominal fistula or gastrointestinal perforation

• No history or evidence of seizures not controlled with standard medical therapy

• No intra-abdominal abscess within the past 28 days

• No active bleeding or pathologic conditions that carry a high risk of bleeding (e.g., bleeding disorder, coagulopathy, or tumor involving major vessels)

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• No significant traumatic injury within the past 28 days

• No concurrent combination antiretroviral therapy for HIV-positive patients

• Recovered from prior surgery

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered

• At least 1 week since prior hormonal therapy

• Concurrent hormone replacement therapy allowed

• At least 3 weeks since any other prior therapy, including immunologic agents

• One additional prior cytotoxic regimen for management of recurrent or persistent endometrial cancer allowed

• Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa

• More than 28 days since prior major surgery or open biopsy

• More than 7 days since prior minor surgery, fine needle aspirates, or core biopsies

• No prior cancer treatment that would preclude study compliance

• No prior noncytotoxic chemotherapy for management of recurrent or persistent endometrial disease

• No prior VEGF Trap or other VEGF pathway-targeted therapy

• More than 5 years since prior radiotherapy to any portion of the abdominal cavity or pelvis except for the treatment of endometrial cancer

• More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin

• Patient must remain free of recurrent or metastatic disease

• More than 5 years since prior chemotherapy for any abdominal or pelvic tumor except for the treatment of endometrial cancer

• More than 3 years since prior adjuvant chemotherapy for localized breast cancer

• Patient must remain free of recurrent or metastatic disease

• Concurrent low-molecular weight heparin allowed for the prevention or treatment of venous thromboembolic disease if condition is considered clinically stable with treatment

• No other concurrent investigational agents

• No concurrent major surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hartford Hospital	Hartford	Connecticut	United States	06102
2	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
3	Washington Hospital Center	Washington	District of Columbia	United States	20010
4	Jupiter Medical Center	Jupiter	Florida	United States	33458
5	Florida Hospital	Orlando	Florida	United States	32803
6	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
7	Northwestern University	Chicago	Illinois	United States	60611
8	University of Illinois	Chicago	Illinois	United States	60612
9	University of Chicago	Chicago	Illinois	United States	60637
10	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
11	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
12	Providence Medical Center	Kansas City	Kansas	United States	66112
13	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
14	Radiation Oncology Center of Olathe	Olathe	Kansas	United States	66061
15	Menorah Medical Center	Overland Park	Kansas	United States	66209
16	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas	United States	66210
17	Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
18	Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
19	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
20	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
21	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49431
22	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
23	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
24	Truman Medical Center	Kansas City	Missouri	United States	64108
25	Saint Luke's Cancer Institute	Kansas City	Missouri	United States	64111
26	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
27	Radiation Oncology Practice Corporation South	Kansas City	Missouri	United States	64114
28	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
29	North Kansas City Hospital	Kansas City	Missouri	United States	64116
30	Research Medical Center	Kansas City	Missouri	United States	64132
31	Radiation Oncology Practice Corporation - North	Kansas City	Missouri	United States	64154
32	Liberty Hospital	Liberty	Missouri	United States	64068
33	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
34	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
35	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
36	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico	United States	87106
37	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
38	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
39	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
40	Gynecologic Oncology Network	Greenville	North Carolina	United States	27834
41	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
42	Case Western Reserve University	Cleveland	Ohio	United States	44106
43	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
44	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
45	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
46	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
47	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
48	Miami Valley Hospital	Dayton	Ohio	United States	45409
49	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
50	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
51	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
52	Cancer Care Associates-Midtown	Tulsa	Oklahoma	United States	74104
53	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
54	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
55	Women and Infants Hospital	Providence	Rhode Island	United States	02905
56	M D Anderson Cancer Center	Houston	Texas	United States	77030
57	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
58	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
59	University of Washington Medical Center	Seattle	Washington	United States	98195
60	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
61	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
62	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
63	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
64	Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
65	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
66	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
67	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Gynecologic Oncology Group

Investigators

• Principal Investigator: Robert Coleman, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00462826
• Other Study ID Numbers: NCI-2009-00597; NCI-2009-00597; CDR0000540237; GOG-0229F; GOG-0229F; U10CA027469
• First Posted: Apr 19, 2007
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma; Endometrial Neoplasms; Recurrence; Aflibercept; Endothelial Growth Factors

Study Results

Participant Flow

Recruitment Details	Patients were accrued to the first stage of accrual from 11/5/2007 to 6/2/2008. Patients were accrued to the second stage between 4/6/2009 and 7/13/2009. They received 4 mg/kg IV of VEGF-Trap every two weeks. One cycle was 28 days.
Pre-assignment Detail	Patients were required to have had one prior chemotherapeutic regimen for the treatment of endometrial carcinoma. Patients entering the study therefore were required to have either persistent or recurrent cancer that was measurable by RECIST.

Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	49
COMPLETED	44
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	44
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.2 (8.4)
Age, Customized (participants) [Number]
40-49 years	3 6.8%
50-59 years	13 29.5%
60-69 years	15 34.1%
70-79 years	12 27.3%
80-89 years	1 2.3%
Sex: Female, Male (Count of Participants)
Female	44 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	44 100%
International Federation of Gynecology and Obstetrics (FIGO) Recurrent/Persistent Disease (participants) [Number]
Number [participants]	44 100%
Cell Type (participants) [Number]
Adenocarcinoma, Unspecified	1 2.3%
Clear Cell Carcinoma	1 2.3%
Endometrioid Adenocarcinoma	23 52.3%
Mucinous Adenocarcinoma	1 2.3%
Mixed Epithelial Carcinoma	6 13.6%
Carcinsarcoma, MMT	1 2.3%
Serous Adenocarcinoma	11 25%
Reason Off Study Therapy (participants) [Number]
Disease Progression	25 56.8%
Refused Further Treatment	1 2.3%
Toxicity as permitted	14 31.8%
Death	3 6.8%
Other	1 2.3%
Tumor Response (participants) [Number]
Partial Response	3 6.8%
Stable Disease	14 31.8%
Increase Disease	16 36.4%
Indeterminate	11 25%

Outcome Measures

1. Primary Outcome

Title	6 Month Progression-free Survival
Description	Number of participants who survived progression-free for more than 6 months.
Time Frame	At 6 monthsEvery other cycle during treatment for the first 6 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	44
Number [participants]	18 40.9%

2. Primary Outcome

Title	Objective Tumor Response (RECIST 1.0)
Description	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time Frame	Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	44
Complete Response	0 0%
Partial Response	3 6.8%

3. Primary Outcome

Title	Number of Participants With Incidence of Adverse Events at Least Possibly Related to Study Agent as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description	Adverse events at least possibly related to the study agent.
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients.

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 3.0)	Grade 2 (CTCAE v 3.0)	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)	Grade 5 (CTCAE v 3.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 3 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 3.0	Number of patients who experienced a grade 5 event using Common Terminology Criteria version 3.0
Measure Participants	44	44	44	44	44	44
Leukopenia	37 84.1%	7 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Thrombocytopenia	36 81.8%	5 NaN	2 NaN	1 NaN	0 NaN	0 NaN
Neutropenia	41 93.2%	0 NaN	1 NaN	1 NaN	1 NaN	0 NaN
Anemia	25 56.8%	9 NaN	9 NaN	1 NaN	0 NaN	0 NaN
Other hematologic	40 90.9%	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Allergy/Immunology	40 90.9%	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Cardiac	23 52.3%	1 NaN	8 NaN	10 NaN	2 NaN	0 NaN
Coagulation	39 88.6%	3 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Constitutional	16 36.4%	13 NaN	12 NaN	3 NaN	0 NaN	0 NaN
Dermatologic	36 81.8%	6 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Endocrine	42 95.5%	2 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Nausea	25 56.8%	12 NaN	4 NaN	3 NaN	0 NaN	0 NaN
Vomiting	32 72.7%	6 NaN	4 NaN	2 NaN	0 NaN	0 NaN
Gastrointestinal	14 31.8%	15 NaN	10 NaN	3 NaN	1 NaN	1 NaN
Genitourinary/renal	41 93.2%	2 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Hemorrhage	36 81.8%	5 NaN	0 NaN	1 NaN	2 NaN	0 NaN
Infection	39 88.6%	0 NaN	3 NaN	2 NaN	0 NaN	0 NaN
Lymphatics	40 90.9%	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Metabolic	27 61.4%	10 NaN	3 NaN	3 NaN	1 NaN	0 NaN
Musculoskeletal	41 93.2%	2 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Neurosensory	38 86.4%	4 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Other neurological	31 70.5%	7 NaN	1 NaN	2 NaN	3 NaN	0 NaN
Ocular/visual	42 95.5%	1 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Pain	13 29.5%	15 NaN	8 NaN	8 NaN	0 NaN	0 NaN
Pulmonary	23 52.3%	13 NaN	4 NaN	3 NaN	1 NaN	0 NaN
Vascular	43 97.7%	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN

4. Secondary Outcome

Title	Duration of Progression-free Survival
Description	Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
Time Frame	Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	44
Median (90% Confidence Interval) [months]	2.9

5. Secondary Outcome

Title	Duration of Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	44
Median (90% Confidence Interval) [months]	14.5

Adverse Events

Time Frame	From the time of study activation until 7-8-2011 when the last form was submitted.
Arm/Group Title	Treatment (Aflibercept)
Arm/Group Description	Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Aflibercept)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Aflibercept)
	Affected / at Risk (%)	# Events
Total	24/44 (54.5%)
Blood and lymphatic system disorders
Neutrophils	1/44 (2.3%)
Cardiac disorders
Hypertension	2/44 (4.5%)
Lt Ventricular Systolic Dysfunction	1/44 (2.3%)
Gastrointestinal disorders
Perforation, Gi - Colon	1/44 (2.3%)
Ileus	1/44 (2.3%)
Obstruction, Gi - Small Bowel Nos	1/44 (2.3%)
General disorders
Fever	1/44 (2.3%)
Death No Ctcae Term - Disease Progression Nos	3/44 (6.8%)
Pain: Pelvis	1/44 (2.3%)
Pain: Chest Wall	1/44 (2.3%)
Metabolism and nutrition disorders
Proteinuria	1/44 (2.3%)
Creatinine	1/44 (2.3%)
Hyperkalemia	1/44 (2.3%)
Nervous system disorders
Neurology - Other	1/44 (2.3%)
Encephalopathy	1/44 (2.3%)
Seizure	1/44 (2.3%)
Cns Ischemia	1/44 (2.3%)
Confusion	1/44 (2.3%)
Vascular disorders
Hemorrhage, Cns	1/44 (2.3%)
Vascular - Other	1/44 (2.3%)
Thrombosis/Thrombus/Embolism	1/44 (2.3%)
Other (Not Including Serious) Adverse Events
	Treatment (Aflibercept)
	Affected / at Risk (%)	# Events
Total	28/44 (63.6%)
Blood and lymphatic system disorders
Platelets	9/44 (20.5%)
Leukocytes	7/44 (15.9%)
Lymphopenia	4/44 (9.1%)
Hemoglobin	22/44 (50%)
Edema: Limb	5/44 (11.4%)
Cardiac disorders
Hypertension	19/44 (43.2%)
Ear and labyrinth disorders
Tinnitus	5/44 (11.4%)
Endocrine disorders
Hot Flashes	3/44 (6.8%)
Eye disorders
Blurred Vision	3/44 (6.8%)
Gastrointestinal disorders
Dysphagia	5/44 (11.4%)
Taste Alteration	3/44 (6.8%)
Mucositis (Functional/Sympt) - Oral Cavity	3/44 (6.8%)
Mucositis (Clinical Exam) - Oral Cavity	11/44 (25%)
Vomiting	12/44 (27.3%)
Anorexia	15/44 (34.1%)
Constipation	16/44 (36.4%)
Nausea	19/44 (43.2%)
Diarrhea	10/44 (22.7%)
General disorders
Weight Loss	3/44 (6.8%)
Fatigue	28/44 (63.6%)
Pain: Head/Headache	17/44 (38.6%)
Pain: Extremity-Limb	5/44 (11.4%)
Pain: Joint	10/44 (22.7%)
Pain: Abdominal Pain Nos	9/44 (20.5%)
Immune system disorders
Rhinitis	5/44 (11.4%)
Infections and infestations
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	5/44 (11.4%)
Metabolism and nutrition disorders
Ast	9/44 (20.5%)
Metabolic/Laboratory - Other	3/44 (6.8%)
Proteinuria	4/44 (9.1%)
Creatinine	10/44 (22.7%)
Hypoalbuminemia	12/44 (27.3%)
Alt	4/44 (9.1%)
Alkaline Phosphatase	9/44 (20.5%)
Hyponatremia	13/44 (29.5%)
Hypocalcemia	10/44 (22.7%)
Hyperkalemia	7/44 (15.9%)
Hyperglycemia	16/44 (36.4%)
Hypokalemia	5/44 (11.4%)
Hypomagnesemia	6/44 (13.6%)
Musculoskeletal and connective tissue disorders
Muscle Weakness - Extremity-Lower	3/44 (6.8%)
Nervous system disorders
Mood Alteration - Depression	9/44 (20.5%)
Neuropathy-Sensory	18/44 (40.9%)
Renal and urinary disorders
Urinary Frequency	5/44 (11.4%)
Respiratory, thoracic and mediastinal disorders
Voice Changes	12/44 (27.3%)
Cough	11/44 (25%)
Dyspnea	14/44 (31.8%)
Skin and subcutaneous tissue disorders
Nail Changes	6/44 (13.6%)
Hair Loss/Alopecia (Scalp Or Body)	7/44 (15.9%)
Rash	6/44 (13.6%)
Vascular disorders
Inr	3/44 (6.8%)
Ptt	3/44 (6.8%)
Hemorrhage, Gu - Vagina	3/44 (6.8%)
Hemorrhage/Pulmonary - Nose	5/44 (11.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.